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Updated: Feb 22, 2026

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy

Published on: October 4, 2019

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Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability

Christian J Braun1, Monica Stanciu1, Paul L Boutz1

  • 1The David H. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

Cancer Cell
|October 3, 2017
PubMed

Insights

Researchers discovered that inhibiting PRMT5, a protein crucial for splicing, effectively suppresses glioblastoma (GBM) growth. This finding reveals a new therapeutic strategy targeting a specific splicing defect in cancer cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
  • Identifying novel therapeutic targets is critical for improving GBM patient outcomes.

Purpose of the Study:

  • To investigate the role of PRMT5 in glioblastoma.
  • To explore PRMT5 inhibition as a potential therapeutic strategy for GBM.

Main Methods:

  • Conducted an in vivo shRNA screen to identify GBM vulnerabilities.
  • Utilized patient-derived xenografts to assess PRMT5 inhibition efficacy.
  • Performed pathway analysis to understand PRMT5's mechanism of action.
  • Investigated the impact of PRMT5 deficiency on detained intron (DI) splicing.

Main Results:

  • PRMT5 knockdown or inhibition significantly suppressed GBM tumor growth in vivo.
  • PRMT5 inhibition led to impaired removal of detained introns (DIs).
  • Disrupted DI splicing resulted in downregulation of proliferation genes, causing cell cycle defects, senescence, and/or apoptosis.
  • Identified a biomarker predicting sensitivity to PRMT5 inhibition.

Conclusions:

  • PRMT5 plays a critical role in regulating DI splicing in glioblastoma.
  • PRMT5-regulated DI splicing represents a novel and exploitable vulnerability in GBM.
  • Targeting PRMT5 offers a promising therapeutic avenue for glioblastoma treatment.
Keywords:
CLNS1AEPZ015666GBMPRMT5RIOK1biomarkersplicing addiction

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